{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:45:03Z","timestamp":1774950303433,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Research and Development, Poland","award":["INNOMED\/I\/11\/NCBR\/2014"],"award-info":[{"award-number":["INNOMED\/I\/11\/NCBR\/2014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Low-THC Cannabis sativa L. extracts are commonly believed to offer potential alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for inflammatory pain management. This study evaluated the anti-inflammatory effects of two C. sativa extracts (Tygra, Dora) and pure cannabidiol (CBD) compared with acetylsalicylic acid (ASA) in a carrageenan-induced rat paw inflammation model. Materials and Methods: Fifty male Wistar rats were randomized into five groups: control, ASA (200 mg\/kg), CBD (20 mg\/kg), Extract B (Tygra), and Extract D (Dora). Treatments were administered intragastrically 30 min after carrageenan injection. Paw volume was measured at 0, 1, 3, 6, and 10 h, and mRNA levels of COX-1, COX-2, TNF\u03b1, NF\u03baB, CB1, and CB2 were quantified by qPCR. Results: Unlike ASA, which reduced paw edema and NF\u03baB expression at 10 h, CBD and both extracts increased edema compared to control. Specifically, Extract D induced greater edema than ASA, upregulated CB1 and CB2 (surpassing ASA CB2 levels), decreased TNF\u03b1, and reduced right-paw COX-2. Extract B increased edema (3 h vs. ASA), increased TNF\u03b1, and showed a positive COX-2\/paw volume correlation. Furthermore, paw volume correlated negatively with CB2 under CBD treatment (which also lowered right-paw COX-2) and positively with COX-1 under ASA treatment. Conclusions: The results indicate that ASA has a clear anti-inflammatory effect, whereas CBD and the hemp extracts fail to inhibit\u2014and may even exacerbate\u2014the inflammatory response. Differences in endocannabinoid and inflammatory gene expression suggest extract composition\u2013dependent modulation mechanisms.<\/jats:p>","DOI":"10.3390\/nu18071106","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"1106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Anti-Inflammatory Effects of Cannabis sativa Extracts via Possible Modulation of mRNA Levels of Inflammatory Cytokines and Cannabinoid Receptors"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-0512","authenticated-orcid":false,"given":"Joanna","family":"Bartkowiak-Wieczorek","sequence":"first","affiliation":[{"name":"Physiology Department, Poznan University of Medical Sciences, 60-179 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-0689","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Kujawski","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-2789","authenticated-orcid":false,"given":"Micha\u0142","family":"Szulc","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-4746","authenticated-orcid":false,"given":"Kamila","family":"Czora-Poczwardowska","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Szymczak","sequence":"additional","affiliation":[{"name":"Physiology Department, Poznan University of Medical Sciences, 60-179 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3858-5809","authenticated-orcid":false,"given":"Julia","family":"Gierszewska","sequence":"additional","affiliation":[{"name":"Student Scientific Society of Physiology, Poznan University of Medical Sciences, 60-179 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Miotk","sequence":"additional","affiliation":[{"name":"Student Scientific Society of Pharmacology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-6523","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Miko\u0142ajczak","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-6558","authenticated-orcid":false,"given":"Edyta","family":"M\u0105dry","sequence":"additional","affiliation":[{"name":"Physiology Department, Poznan University of Medical Sciences, 60-179 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2815-0372","authenticated-orcid":false,"given":"Teresa","family":"Grzelak","sequence":"additional","affiliation":[{"name":"Physiology Department, Poznan University of Medical Sciences, 60-179 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121134","DOI":"10.1016\/j.jep.2025.121134","article-title":"Phytocannabinoids as anti-inflammatory agents: Synergistic effects when combined with Cannabis sativa L. matrices","volume":"360","author":"Strnad","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Masteikova, R., Lazauskas, R., and Bernatoniene, J. (2022). Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation. Antioxidants, 11.","DOI":"10.3390\/antiox11040660"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4103\/sni.sni_45_18","article-title":"Review of the neurological benefits of phytocannabinoids","volume":"9","author":"Maroon","year":"2018","journal-title":"Surg. Neurol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"NS20200080","DOI":"10.1042\/NS20200080","article-title":"Cannabidiol modulation of oxidative stress and signalling","volume":"5","author":"Pereira","year":"2021","journal-title":"Neuronal Signal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.bmc.2015.01.059","article-title":"Cannabidiol (CBD) and its analogs: A review of their effects on inflammation","volume":"23","author":"Burstein","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"680","DOI":"10.12688\/f1000research.134023.1","article-title":"Anti-inflammatory effects of oral cannabidiol in rat models","volume":"12","author":"Bunman","year":"2023","journal-title":"F1000Research"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Szalata, M., Dreger, M., Zieli\u0144ska, A., Banach, J., Szalata, M., and Wielgus, K. (2022). Simple Extraction of Cannabinoids from Female Inflorescences of Hemp (Cannabis sativa L.). Molecules, 27.","DOI":"10.3390\/molecules27185868"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska, A., da Ana, R., Fonseca, J., Szalata, M., Wielgus, K., Fathi, F., Oliveira, M.B.P.P., Staszewski, R., Karczewski, J., and Souto, E.B. (2023). Phytocannabinoids: Chromatographic Screening of Cannabinoids and Loading into Lipid Nanoparticles. Molecules, 28.","DOI":"10.3390\/molecules28062875"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bartkowiak-Wieczorek, J., Jamka, M., Kujawski, R., Ho\u0142ysz, M., Bienert, A., Czora-Poczwardowska, K., Szulc, M., Miko\u0142ajczak, P., Bogacz, A., and Wizner, A.M. (2025). Cannabis sativa L. Extract Increases COX-1, COX-2 and TNF-\u03b1 in the Hippocampus of Rats with Neuropathic Pain. Molecules, 30.","DOI":"10.3390\/molecules30010194"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bednarczyk-Cwynar, B., Wachowiak, N., Szulc, M., Kaminska, E., Bogacz, A., Bartkowiak-Wieczorek, J., Zaprutko, L., and Mikolajczak, P.L. (2016). Strong and long-lasting antinociceptive and anti-inflammatory conjugate of naturally occurring oleanolic acid and aspirin. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00202"},{"key":"ref_13","unstructured":"Columbia University Mailman School of Public Health (1980). Based on Snedecor & Cochran, Statistical Methods, Columbia University Mailman School of Public Health. [7th ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/sj.bjp.0705650","article-title":"Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression","volume":"142","author":"Posadas","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1055\/s-0036-1582132","article-title":"Stages of the inflammatory response in pathology and tissue repair after intracerebral hemorrhage","volume":"36","author":"Askenase","year":"2016","journal-title":"Semin. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00210-004-0871-3","article-title":"Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of Cannabis, in acute carrageenan-induced inflammation in the rat paw","volume":"369","author":"Costa","year":"2004","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/sj.bjp.0706775","article-title":"Relevance of tumour necrosis factor-\u03b1 for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw","volume":"148","author":"Rocha","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.neuropharm.2016.12.008","article-title":"Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists","volume":"116","author":"Grenald","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB2 receptor and its role as a regulator of inflammation","volume":"73","author":"Turcotte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/1570159X17666190903103923","article-title":"The \u201cEntourage Effect\u201d: Terpenes Coupled with cannabinoids for the treatment of mood disorders and anxiety disorders","volume":"18","author":"Ferber","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.pharmtox.38.1.97","article-title":"Cyclooxygenases 1 and 2","volume":"38","author":"Vane","year":"1998","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1046\/j.1365-2036.1997.00247.x","article-title":"Aspirin causes rapid up-regulation of cyclo-oxygenase-2 expression in the stomach of rats","volume":"11","author":"Davies","year":"1997","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9247","DOI":"10.1038\/sj.onc.1208169","article-title":"Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation","volume":"23","author":"Takada","year":"2004","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28028","DOI":"10.1074\/jbc.M001387200","article-title":"Feedback control of cyclooxygenase-2 expression through PPARgamma","volume":"275","author":"Inoue","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.tips.2009.07.006","article-title":"Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb","volume":"30","author":"Izzo","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1089\/can.2018.0073","article-title":"Immune Responses Regulated by Cannabidiol","volume":"5","author":"Nichols","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0304-3959(97)00213-3","article-title":"Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors","volume":"75","author":"Richardson","year":"1998","journal-title":"Pain"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Atalay, S., Jarocka-Karpowicz, I., and Skrzydlewska, E. (2019). Antioxidative and anti-inflammatory properties of Cannabidiol. Antioxidants, 9.","DOI":"10.3390\/antiox9010021"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/9550","article-title":"Inducible cyclooxygenase may have anti-inflammatory properties","volume":"5","author":"Gilroy","year":"1999","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential Cannabis synergy and phytocannabinoid-terpenoid entourage effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102047","DOI":"10.1016\/j.pupt.2021.102047","article-title":"The anti-inflammatory effects of cannabidiol and cannabigerol alone, and in combination","volume":"69","author":"Horniman","year":"2021","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1089\/can.2020.0105","article-title":"The Effects of Cannabinoids on Pro- and Anti-Inflammatory Cytokines: A Systematic Review of In Vivo Studies","volume":"6","author":"Henshaw","year":"2021","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1089\/can.2018.0014","article-title":"The anti-Inflammatory properties of terpenoids from Cannabis","volume":"3","author":"Gallily","year":"2018","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4236\/pp.2015.62010","article-title":"Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol","volume":"6","author":"Gallily","year":"2015","journal-title":"Pharmacol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.1523\/JNEUROSCI.0504-08.2008","article-title":"TRPV2 Is Activated by Cannabidiol and Mediates CGRP Release in Cultured Rat Dorsal Root Ganglion Neurons","volume":"28","author":"Qin","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1111\/bph.15208","article-title":"Cannabinoid control of neurogenic inflammation","volume":"177","author":"McKenna","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113458","DOI":"10.1016\/j.fct.2022.113458","article-title":"Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis sativa employing human primary leukocytes","volume":"170","author":"Blevins","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1021\/acschemneuro.0c00075","article-title":"Anti-inflammatory Potential of Terpenes Present in Cannabis sativa L.","volume":"11","author":"Downer","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Andr\u00e9, R., Gomes, A.P., Pereira-Leite, C., Marques-da-Costa, A., Monteiro Rodrigues, L., Sassano, M., Rijo, P., and Costa, M.d.C. (2024). The Entourage Effect in Cannabis Medicinal Products: A Comprehensive Review. Pharmaceuticals, 17.","DOI":"10.20944\/preprints202409.1225.v1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1089\/can.2023.0052","article-title":"Does the \u2018Entourage Effect\u2019 in Cannabinoids Exist? A Narrative Scoping Review","volume":"9","author":"Simei","year":"2024","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/apa.13384","article-title":"Understanding type I and type II errors, statistical power and sample size","volume":"105","author":"Akobeng","year":"2016","journal-title":"Acta Paediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21134","DOI":"10.1073\/pnas.1202906109","article-title":"Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor","volume":"109","author":"Pamplona","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:45:37Z","timestamp":1774946737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18071106"],"URL":"https:\/\/doi.org\/10.3390\/nu18071106","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]}}}